Characterising neurological time series data using biologically motivated networks of coupled discrete maps.

Artificial biochemical networks (ABNs) are a class of computational dynamical system whose architectures are motivated by the organisation of genetic and metabolic networks in biological cells. Using evolutionary algorithms to search for networks with diagnostic potential, we demonstrate how ABNs can be used to carry out classification when stimulated with time series data collected from human subjects with and without Parkinson's disease. Artificial metabolic networks, composed of coupled discrete maps, offer the best recognition of Parkinsonian behaviour, achieving accuracies in the region of 90%. This is comparable to the diagnostic accuracies found in clinical diagnosis, and is significantly higher than those found in primary and non-expert secondary care. We also illustrate how an evolved classifier is able to recognise diverse features of Parkinsonian behaviour and, using perturbation analysis, show that the evolved classifiers have interesting computational behaviours.

Depression in patients with Parkinson's disease: identification and treatment.

Recognizing depression in Parkinson's disease can be problematic but since it has such a significant impact on the quality of life in these patients and is easily treatable the value of therapeutic intervention should not be underestimated.

The case of stainless statins.

Two cases of hypercholesterolaemic patients are presented in whom raised plasma creatine kinase was noted during treatment with statins. The plasma creatine kinase failed to fall following cessation of therapy. Further investigation revealed the aetiology of the raised plasma creatine kinase to be due to previously undiagnosed glycogen storage diseases (McArdle's and Pompe's diseases).

Randomised controlled trial of atraumatic versus standard needles for diagnostic lumbar puncture.

OBJECTIVE: To compare the ease of use of atraumatic needles with standard needles for diagnostic lumbar puncture and the incidence of headache after their use. DESIGN: Double blind, randomised controlled trial. SETTING: Investigation ward of a neurology unit in a university hospital. PARTICIPANTS: 116 patients requiring elective diagnostic lumbar puncture. INTERVENTIONS: Standardised protocol for lumbar puncture with 20 gauge atraumatic or standard needles. OUTCOME MEASURES: The primary end point was intention to treat analysis of incidence of moderate to severe headache, assessed at one week by telephone interview. Secondary end points were incidence of headache at one week analysed by needle type, ease of use by operator according to a visual analogue scale, incidence of backache, and failure rate of puncture. RESULTS: Valid outcome data were available for 97 of 101 patients randomised. Baseline characteristics were matched except for higher body mass index in the standard needle group. By an intention to treat analysis the absolute risk of moderate to severe headache with atraumatic needles was reduced by 26% (95% confidence interval 6% to 45%) compared with standard needles, but there was a non-significantly greater absolute risk of multiple attempts at lumbar puncture (14%, -4% to 32%). Higher body mass index was associated with an increased failure rate with atraumatic needles, but the reduced incidence of headache was maintained. The need for medical interventions was reduced by 20% (1% to 40%). CONCLUSIONS: Atraumatic needles significantly reduced the incidence of moderate to severe headache and the need for medical interventions after diagnostic lumbar punctures, but they were associated with a higher failure rate than standard needles.

Ear clicks in palatal tremor caused by activity of the levator veli palatini.

We describe a patient who developed palatal tremor and presented with ear clicks that appeared to originate from activity of the levator veli palatini and not the tensor veli palatini. This was treated with botulinum toxin. We discuss the motor innervation of the palate in the context of our case, our findings in terms of classification, and how the lower cranial nerve nuclei are involved in the etiology of palatal tremor.

Unique presentation of a prolapsed thoracic disk: Lhermitte's symptom in a golf player.

We describe a man with a thoracic disk prolapse whose major manifestation for 10 years was Lhermitte's symptom precipitated by a rotatory movement of the thoracic spine during during the golf swing.

Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants.

The development and utilization of a tissue culture system for the analysis of quiescent, nonreplicating herpes simplex virus type 1 (HSV-1) genomes is described. It was demonstrated previously that the HSV-1 Vmw65 mutant in1814, which is impaired for immediate early (IE) transcription, was retained for many days in human fetal lung (HFL) fibroblasts in a quiescent 'latent' state. Molecular analysis of the viral genome was not possible, however, due to residual expression of IE proteins and consequent cytotoxicity at high m.o.i. In the study reported here, IE transcription was reduced further by pretreatment of cells with interferon-alpha (IFN-alpha) and by the use of mutant in1820, a derivative of in1814 in which the Vmw110 promoter was replaced by the Moloney murine leukaemia virus (Momulv) enhancer. The Momulv enhancer was not expressed under IE conditions; thus in1820 was more impaired for replication than in1814 and behaved as if deficient for both Vmw65 and Vmw110. In cells pretreated with IFN-alpha and subsequently infected with in1820 cytotoxicity was overcome, enabling a tissue culture system to be developed in which all cells stably retained at least one quiescent viral genome. To assist the analysis of gene expression, in1820 was further modified by insertion of the Escherichia coli lacZ gene controlled by the human cytomegalovirus enhancer (mutant in1883) or the HSV-1 immediate early Vmw110 promoter (in1884). Expression of beta-galactosidase was not detected after infection of IFN-alpha-pretreated cells with in1883 or in1884 but could be induced in almost all cells containing a viral genome, by superinfection of cultures. In1820-derived viruses were retained for at least 9 days and were not reactivated by subculture of cells. A regular arrangement of nucleosomes, as found in cellular chromatin, was not detected on the viral genome at the thymidine kinase locus. The non-linear genome was a template for reactivation with no requirement for prior conversion to a linear form. A small number of remaining linear genomes resulted from incomplete uncoating of input virus.

Herpes simplex virus latency in tissue culture cells.

We have developed tissue culture systems which mimic certain aspects of herpes simplex virus (HSV) latency, in order to facilitate molecular studies of the phenomenon. The initial approach utilised incubation at 42 degrees C to suppress virus replication and establish stable latency after infection of human fibroblasts at low multiplicity with HSV-2. Latent virus was reactivated efficiently by superinfection of cultures with HSV-1 or human cytomegalovirus. Improvement of the system was achieved by use of the HSV-1 mutant in1814, which has a 12 base pair insertion in the coding sequences for the transactivating protein Vmw65 (VP16). Upon infection with in1814 at 42 degrees, or 37 degrees, it was possible to obtain cultures in which up to 21% of cells contained a viral genome. More recent modifications include the use of mutant in1820 (a derivative of in 1814) and pretreatment of cells with interferon alpha, which enable latency to be established in approximately 100% of cells. A system has therefore been developed that is suitable for the analysis of gene expression and genome structure during latency and reactivation.